A series of studies were conducted to understand the effect of naturally occuring mutations in the lipopolysaccharide of Neisseria meningitidis, henceforth referred to as lipoologosaccharide (LOS), on virulence and natural proteccion against meningococcal disease.The effect of meningococcal cell associated sialic acid on ability of isogenic variants N. meningitidis to become serum resistant (SR) was eamined by ELISA before and after neuraminidase treatment. Removal of sialic acid with neuraminidase restores Mab binding to My-28 and 3 F11 that recognized the lacto-N-neotetraose (LNnT) LOS epitope, usually masked by sialic acid when present in meningococcal and gonococcal strains. Wild type BB 305-4 and 44/76-1 (both SR) had the carbohydrate sequence LNnT, although the former was not sialylated. The terminal Gal that is the acceptor for sialylation is either absent or blocked in isogenic mutants that were unable to bind the two Mab~s.To analyse whether the isogenic variations in the length of LPS core sugar modifies accessibility of antibody to OMV, ELISA was performed with OMV and whole bacteria. All mutants showed higher antibody binding than the wild types, especially variants BB 305-5 LOS. The reduction in OMV antibody titers was between 24 to 40%, suggesting the OMV results were due to uncovering of protein epitopes with shorter LOS mutants. Assays using OMV and whole cell were in agreement.These results suggest that the natural mutation in LOS of Nesseria meningitidis affect their virulence in that there are alterations from serum resistant to serum sensitive. The loss of certain epitopes exposes others thus the bacteria becomes more sensible to the activity of serum, by bactericidal antibodies directed to outer membrane proteins and LOS.